Access to the Akuammiline Family of Alkaloids: Total Synthesis of (+)-Scholarisine A

The planning and implementation of an enantioselective total synthesis of (+)-scholarisine A is presented. Key tactics employed include a novel cyclization, consisting of a nitrile reduction coupled with concomitant addition of the resultant amine to an epoxide; a modified Fischer indolization; an oxidative lactonization of a diol in the presence of an indole ring; and a late-stage cyclization to complete the caged ring scaffold. The development of a possible retro-biosynthetic approach to other members of the akuammiline alkaloid family is also described.